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TitleAn epitope-enriched immunogen expands responses to a conserved viral site.
Journal, issue, pagesCell Rep, Vol. 41, Issue 6, Page 111628, Year 2022
Publish dateNov 8, 2022
AuthorsTimothy M Caradonna / Larance Ronsard / Ashraf S Yousif / Ian W Windsor / Rachel Hecht / Thalia Bracamonte-Moreno / Anne A Roffler / Max J Maron / Daniel P Maurer / Jared Feldman / Elisa Marchiori / Ralston M Barnes / Daniel Rohrer / Nils Lonberg / Thomas H Oguin / Gregory D Sempowski / Thomas B Kepler / Masayuki Kuraoka / Daniel Lingwood / Aaron G Schmidt /
PubMed AbstractPathogens evade host humoral responses by accumulating mutations in surface antigens. While variable, there are conserved regions that cannot mutate without compromising fitness. Antibodies targeting ...Pathogens evade host humoral responses by accumulating mutations in surface antigens. While variable, there are conserved regions that cannot mutate without compromising fitness. Antibodies targeting these conserved epitopes are often broadly protective but remain minor components of the repertoire. Rational immunogen design leverages a structural understanding of viral antigens to modulate humoral responses to favor these responses. Here, we report an epitope-enriched immunogen presenting a higher copy number of the influenza hemagglutinin (HA) receptor-binding site (RBS) epitope relative to other B cell epitopes. Immunization in a partially humanized murine model imprinted with an H1 influenza shows H1-specific serum and >99% H1-specific B cells being RBS-directed. Single B cell analyses show a genetically restricted response that structural analysis defines as RBS-directed antibodies engaging the RBS with germline-encoded contacts. These data show how epitope enrichment expands B cell responses toward conserved epitopes and advances immunogen design approaches for next-generation viral vaccines.
External linksCell Rep / PubMed:36351401 / PubMed Central
MethodsEM (single particle)
Resolution3.36 - 5.0 Å
Structure data

EMDB-26604: H1 Solomon Islands 2006 hemagglutinin in complex with Ab111
Method: EM (single particle) / Resolution: 5.0 Å

EMDB-26605, PDB-7umm:
H1 Solomon Islands 2006 hemagglutinin in complex with Ab109
Method: EM (single particle) / Resolution: 3.36 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • influenza a virus (a/solomon islands/3/2006(h1n1))
  • mus musculus (house mouse)
KeywordsVIRAL PROTEIN / influenza / antibody / vaccine

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